The second-largest, second-deadliest Ebola outbreak in history has spread to a major city.

Butembo, a bustling city of almost a million people in the eastern Democratic Republic of Congo, is reporting an increasing number of cases of Ebola virus disease in the country’s current epidemic.

There has been a “significant increase” in infections there over the past three weeks, with a total of 25 confirmed cases thus far, according to Thursday’s bulletin from the country’s health ministry.

Butembo is a key trading and transport hub with links to other major cities in the country as well as to neighboring Uganda. It’s about two times the size of the city of Beni, the outbreak’s epicentre, and is located just 35 miles away.

The health ministry said the “high density and mobility” of Butembo’s population presents new challenges to containment efforts, already complicated by sporadic rebel attacks on remote villages in and around Beni.

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Since the outbreak was declared on August 1, a total of 471 people have reported symptoms of hemorrhagic fever in the country’s eastern provinces of North Kivu and Ituri, which share borders with Rwanda, Uganda and South Sudan.

Among those cases, 423 have tested positive for Ebola virus disease, which causes an often-deadly type of hemorrhagic fever, according to the health ministry.

There have been 273 deaths thus far, including 225 people who died from confirmed cases of Ebola. The other deaths are from probable cases of Ebola, the ministry said.

The ongoing outbreak is one of the world’s worst, second only to the 2014-2016 outbreak in multiple West African nations that infected 28,652 people and killed 11,325, according to data from the US Centres for Disease Control and Prevention.

Ebola is endemic to the Democratic Republic of the Congo. This is the 10th outbreak and the worst the country has seen since 1976, the year that scientists first identified the deadly virus near the eponymous Ebola River.

“No other epidemic in the world has been as complex as the one we are currently experiencing,” the Democratic Republic of the Congo’s health minister, Dr. Oly Ilunga Kalenga, said in a statement last month.